Effects of an endogenous anxiolytic adrenal steroid, alpha-THDOC, on non-opioid defeat analgesia in male mice: interaction with Ro15-1788

Abstract

The effects of the putative anxiolytic adrenal steroid, 3α, 5α-tetrahydro deoxycorticosterone (α-THDOC), on non-opioid defeat analgesia in male mice were examined. Although devoid of intrinsic activity on the tail-flick assay, 5 mg/kg α-THDOC was found to significantly attenuate the analgesic consequences of defeat experience; lower (2.5 mg/kg) and higher (10-20 mg/kg) doses were ineffective. The β-isomer of THDOC also significantly reduced defeat analgesia, but only at the highest dose tested (20 mg/kg). Control experiments demonstrated that 5 per cent ethanol, which was employed as a vehicle for the steroids, was without effect per se on basal nociception and, over the limited dose range of 5-10 per cent, did not alter defeat analgesia. Finally, the benzodiazepine receptor antagonist, Ro15-1788 (5 mg/kg) failed to influence the inhibitory effects of either THDOC isomer. Results are discussed in relation to the potential modulation of this form of adaptive pain inhibition by adrenal steroids which influence the GABA receptor-coupled chloride ionophore.